Involvement of Prostaglandins in the Pathophysiology of Endometriosis

Prostaglandins are bioactive lipids that possess multiple and diverse functions. In reproductive biology, they are involved in the regulation of ovulation, in endometrial physiology and in the process of menstruation. Furthermore, cyclooxygenases (COX) levels, which are key enzymes for the synthesis of prostaglandins, have been found to be elevated in pathologic, tumoral and inflammatory processes. In endometriosis, prostaglandins are not only implicated in pain, but they are also critical for the establishment as well as for the development of the disease. The high levels of prostaglandin E2 (PGE2) found in the peritoneal fluid from patients with endometriosis, not only favor cellular proliferation by stimulating the activity of aromatase with the consequent estrogen production, but also these estrogens are responsible for enhancing PGE2 synthesis by stimulating COX-2 activity. PGE2 also stimulates angiogenesis and is implicated in the peritoneal immunologic alterations observed in endometriosis. COX-2 inhibitors were and are used in a vast number of preclinical and clinical studies in different types of cancer. In studies conducted both in vitro and in vivo, we have demonstrated that the selective COX-2 inhibitor, celecoxib, was efficient in inhibiting experimental endometriosis. It is important to search for new horizons in endometriosis treatment. Prostaglandins and the enzymes in charge of their synthesis, COXs, represent an attractive target for developing new therapies that attack directly the molecules involved in the causes of this pathology.Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients

Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium.Fil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vighi, Susana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Alfie, Margarita. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Irigoyen, Marcela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Etchepareborda, Juan J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentin

Growth of endometriotic lesions.

<p>Lesion size (%) of endometriotic lesions at day 14 after transplantation of endometrial fragments into the dorsal skinfold chambers of vehicle-treated controls (white bar; n = 6) and 4-MU-treated (20mg/kg: grey bar, n = 8; 80mg/kg: black bar, n = 7) BALB/c mice, as assessed by intravital fluorescence microscopy and computer-assisted image analysis. Means ± SEM. p>0.05.</p

Vascularization of endometriotic lesions in the skinold chamber.

<p>(A, B) Vascularized area (%) (A) and functional microvessel density (cm/cm²) (B) of developing endometriotic lesions in dorsal skinfold chambers of vehicle-treated controls (white circles; n = 6) and 4-MU-treated (20mg/kg: grey circles, n = 8; 80mg/kg: black circles, n = 7) BALB/c mice, as assessed by intravital fluorescence microscopy and computer-assisted image analysis. Means ± SEM. *p<0.05 vs. control; ^#p<0.05 vs. 20mg/kg 4-MU; ^ap<0.05 vs. d0 and d3; ^bp<0.05 vs. d0, d3 and d6; ^cp<0.05 vs. d0, d3, d6 and d10. (C-E) Intravital fluorescent microscopic images of endometriotic lesions (borders marked by dotted line) at day 10 after transplantation of endometrial fragments into the dorsal skinfold chamber of a vehicle-treated control (C), a 20mg/kg 4-MU-treated (D) and an 80mg/kg 4-MU-treated (E) BALB/c mouse. Blue light epi-illumination with contrast enhancement by 5% FITC-labeled dextran 150,000 i.v. Scale bar: 200μm.</p